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In the build up to this year’s Stand Up To Cancer, we’re running a series of posts that focus on the science that is happening around the country thanks to your generous donations and amazing fundraising. For the third instalment, we’re dedicating a post in our Science Snaps series to research that’s tracking cancer cells’ shape-shifting abilities.
In the early 1990s, one of the biggest movie blockbusters was Terminator 2. In the film, the villainous T-1000 was able to change its shape to relentlessly pursue the heroes.
And just like the Terminator, cancer cells can shape-shift to spread around the body and evade treatment. At The Institute of Cancer Research in London, Dr Chris Bakal’s team is working out how cancer cells do this.
Their hope is that by figuring out which molecular or genetic factors control cancer cell shape, they may reveal clues around how to stop them in their tracks.
Changes to important genes can have a surprisingly large effect on cell shape and behaviour.
The picture below shows several clusters of specialised breast cells, which form the milk glands.
In the top of the picture, normal cells form a tight clustered unit as they are supposed to. But the clump of cells at the bottom is beginning to spread out.
These cells that are spreading out have been prevented from making a single molecule, called JAM3, which helps cells stick together. The gene that produces JAM3 is known as a tumour suppressor gene, meaning that cells can become cancerous when it doesn’t work properly.
The absence of this gene results in a striking change in cell appearance, and the cells move from their normal location and begin to spread. A process that’s mirrored in some cancer cells.
Understanding how and why cell shape changes happen could help doctors to spot which cancer genes are active, potentially helping them to make decisions about treatment.
Cancer cells also change shape to adapt to new surroundings.
Cell shape depends on the tissue in the body they reside in. Stiff tissues such as bone require long spindle-shaped cells, while softer tissues are usually home to round cells.
Melanoma, the deadliest form of skin cancer, is notorious for its ability to spread.
“Melanoma cancer cells are some of the most difficult to treat,” says Bakal. “And this is partly because they are masters of disguise, able to change their shape very easily to invade just about any tissue in the body.”
The cancer cells can adopt the appearance of other cells so they can blend in with different tissue.
Understanding what molecules these cancer cells use to change how they look could reveal new ways to stop them doing so.
A cell’s shape can also be affected by its environment.
The picture below shows a mouse tumour, with the cancer cells (shown in green) creating fibrous strands of a molecule called collagen (in purple).
Collagen acts as scaffolding for a growing tumour, making it easier for cancer cells to move around and gain access to nutrients and oxygen.
“When we think about cancer cells, we forget that tumours are not just a collection of single cells,” says Bakal. “They are part of an ‘ecosystem’ of different cell types, including blood vessels, stromal (connective tissue) cells and support structures.
“Like a spider weaving a web, cancer cells can create a nest of collagen around them. Cancer cells use this collagen as scaffolding to grow and move, or even trap healthy cells to provide them with the nutrients they need.”
Collagen can also provide protection, making it more difficult for drugs or immune cells to reach the tumour.
When this happens, it’s not just the cancer cells that are changing shape – the entire tissue is being remade.
So how can we use this knowledge to help patients?
While we have learned a great deal about cancer from genetics, we may have underestimated the impact that physical forces have on cancer cells
– Dr Chris Bakal
It’s important to remember that cell shape is linked to how cells behave.
By understanding the mechanisms underpinning cell shape, researchers could be able to tell just by looking under a microscope which genes may be disrupted or how a cancer cell is likely to behave.
One of the hopes of Bakal’s research is to find ways to freeze cancer cells certain shapes – preventing them from spreading, and setting them up to receive treatment.
“In fact, one class of chemotherapy drugs, called taxanes, may already do this,” says Dr Bakal.
Taxanes stop cells from creating microtubules, which along with other proteins, make up the internal ‘skeleton’ of a cell. Microtubules pull apart DNA when the cell divides, as well as helping cells to move.
The aim of this treatment is to stop cancer cells multiplying. But, according to Bakal, it might also prevent them from adopting the shapes they need to spread.
“While we have learned a great deal about cancer from genetics, we may have underestimated the impact that physical forces have on cancer cells,” says Bakal.
“I don’t think we fully appreciate how a better knowledge of this could help us treat patients better and monitor their recovery.”
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